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Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells

Oncogene volume 28, pages 4364–4374 (2009)Cite this article

Abstract

Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor, which is essential for the proliferation/maintenance of hematopoietic stem cells (HSCs). Aberrant expression of Evi-1 has been frequently found in myeloid leukemia, and is associated with a poor patient survival. Recently, we reported candidate target genes of Evi-1 shared in HSCs and leukemic cells using gene expression profiling analysis. In this study, we identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a target gene of Evi-1. Overexpression of Evi-1 increased Pbx1 expression in hematopoietic stem/progenitor cells. An analysis of the Pbx1 promoter region revealed that Evi-1 upregulates Pbx1 transcription. Furthermore, reduction of Pbx1 levels through RNAi-mediated knockdown significantly inhibited Evi-1-induced transformation. In contrast, knockdown of Pbx1 did not impair bone marrow transformation by E2A/HLF or AML1/ETO, suggesting that Pbx1 is specifically required for the maintenance of bone marrow transformation mediated by Evi-1. These results indicate that Pbx1 is a target gene of Evi-1 involved in Evi-1-mediated leukemogenesis.

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Acknowledgements

We thank T Kitamura for Plat-E packaging cells and pMYs-IG retrovirus vector, H Nakauchi and M Onodera for pGCDNsam-eGFP retroviral vector, T Inaba for E2A/HLF cDNA, SW Hiebert for AML1/ETO cDNA, D Bohmann for c-Jun cDNA, Y Shimamura for expert technical assistance, and KYOWA KIRIN for cytokines. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and by Health and Labour Sciences Research grants from Ministry of Health, Labour and Welfare.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate school of Medicine, University of Tokyo, Tokyo, Japan

    M Shimabe, S Goyama, N Watanabe-Okochi, A Yoshimi, M Ichikawa, Y Imai & M Kurokawa

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  1. M Shimabe
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  2. S Goyama
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  3. N Watanabe-Okochi
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Correspondence to M Kurokawa.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Shimabe, M., Goyama, S., Watanabe-Okochi, N. et al. Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells. Oncogene 28, 4364–4374 (2009). https://doi.org/10.1038/onc.2009.288

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